The present invention is generally directed to the treatment of neurodegenerative disorders, and more particularly to a method of ameliorating or abrogating the effects of Huntington's disease (HD) by using coenzyme Q10.
Huntington's disease (HD) is a progressive and fatal neurological disorder that is caused by an expanded CAG repeat in a gene coding for a protein of unknown function, huntingtin. There are no current drug therapies proven to help ameliorate or abrogate the disease process in HD. Although the exact cause of the selective neuronal death in HD remains unknown, it has been postulated that aberrant protein-protein interactions, including aggregation of the mutant huntingtin protein, may be toxic to neurons and lead to oxidative stress, mitochondrial dysfunction, apoptosis, energy metabolism defects, and excitotoxicity.
Coenzyme Q10 (CoQ10) or ubiquinone is essentially a vitamin or vitamin-like substance. It is found naturally in foods, and is also sometimes synthesized in the body. Coenzymes are cofactors upon which the comparatively large and complex enzymes depend for their function. Coenzyme Q10 is the coenzyme for at least three mitochondrial enzymes (complexes I, II, and III) as well as enzymes in other parts of the cell. Mitochondrial enzymes are essential for the production of the high-energy phosphate, adenosine triphosphate (ATP) upon which all cellular functions depend.
There is substantial evidence that bioenergetic defects may play a role in the pathogenesis of HD. A possible therapy for diseases in which there is defective energy metabolism is to administer the mitochondrial cofactor coenzyme Q10(CoQ10). We have previously demonstrated that oral administration of CoQ10 (400 mg/kg) was neuroprotective in R6/2 mice (14.5% survival extension).
In my co-pending application Ser. Nos. 60/545,532, filed Feb. 19, 2004, and 11/058,297, filed Feb. 16, 2005, both entitled METHOD OF AMELIORATING OR ABROGATING THE EFFECTS OF A NEURODEGENERATIVE DISORDER, SUCH AS HUNTINGTON'S DISEASE, BY SODIUM BUTYRATE CHEMOTHERAPY (both hereby incorporated herein in their entirety by reference) the effects of intraperitoneal administration of histone deacetylase (HDAC) inhibitor, such as sodium butyrate, on HD pathogenesis was shown. The present invention is directed to the effects of coenzyme Q10 on HD pathogenesis.